Drug delivery systems based on polyethylene glycol hydrogels for enhanced bone regeneration

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Abstract

Drug delivery systems composed of osteogenic substances and biological materials are of great significance in enhancing bone regeneration, and appropriate biological carriers are the cornerstone for their construction. Polyethylene glycol (PEG) is favored in bone tissue engineering due to its good biocompatibility and hydrophilicity. When combined with other substances, the physicochemical properties of PEG-based hydrogels fully meet the requirements of drug delivery carriers. Therefore, this paper reviews the application of PEG-based hydrogels in the treatment of bone defects. The advantages and disadvantages of PEG as a carrier are analyzed, and various modification methods of PEG hydrogels are summarized. On this basis, the application of PEG-based hydrogel drug delivery systems in promoting bone regeneration in recent years is summarized. Finally, the shortcomings and future developments of PEG-based hydrogel drug delivery systems are discussed. This review provides a theoretical basis and fabrication strategy for the application of PEG-based composite drug delivery systems in local bone defects.

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Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects

Xiaojin Zhang, Yan-Yan Li, Y. Chen … (2016)

MicroRNAs (miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a ‘double-shell’ miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds that spatially control the release of miR-26a. This technology is used to regenerate critical-sized bone defects in osteoporotic mice by targeting Gsk-3β to activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based miRNA therapy for tissue engineering.

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Injectable and thermo-sensitive PEG-PCL-PEG copolymer/collagen/n-HA hydrogel composite for guided bone regeneration.

ShaoZhi Fu, PeiYan Ni, BeiYu Wang … (2012)

A novel three-component biomimetic hydrogel composite was successfully prepared in this study, which was composed of triblock PEG-PCL-PEG copolymer (PECE), collagen and nano-hydroxyapatite (n-HA). The microstructure and thermo-responsibility of the obtained PECE/Collagen/n-HA hydrogel composite were characterized. Scanning electronic microscopy (SEM) showed that the composite exhibited an interconnected porous structure. The rheological analysis revealed that the composite existed good thermo-sensitivity. In vivo biocompatibility and biodegradability was investigated by implanting the hydrogel composite in muscle pouches of rats for 3, 7, and 14 days. Moreover, the osteogenic capacity was evaluated by means of implanting the composite material in cranial defects of New Zealand White rabbits for 4, 12 and 20 weeks. In vivo performances confirmed that the biodegradable PECE/Collagen/n-HA hydrogel composite had good biocompatibility and better performance in guided bone regeneration than the self-healing process. Thus the thermal-response PECE/Collagen/n-HA hydrogel composite had the great potential in bone tissue engineering.

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Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities

Amy Y. Clark, Karen E Martin, José García … (2020)

Stem cell therapies are limited by poor cell survival and engraftment. A hurdle to the use of materials for cell delivery is the lack of understanding of material properties that govern transplanted stem cell functionality. Here, we show that synthetic hydrogels presenting integrin-specific peptides enhance the survival, persistence, and osteo-reparative functions of human bone marrow-derived mesenchymal stem cells (hMSCs) transplanted in murine bone defects. Integrin-specific hydrogels regulate hMSC adhesion, paracrine signaling, and osteoblastic differentiation in vitro. Hydrogels presenting GFOGER, a peptide targeting α2β1 integrin, prolong hMSC survival and engraftment in a segmental bone defect and result in improved bone repair compared to other peptides. Integrin-specific hydrogels have diverse pleiotropic effects on hMSC reparative activities, modulating in vitro cytokine secretion and in vivo gene expression for effectors associated with inflammation, vascularization, and bone formation. These results demonstrate that integrin-specific hydrogels improve tissue healing by directing hMSC survival, engraftment, and reparative activities.

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Author and article information

Contributors

Yutao Cui: URI : https://loop.frontiersin.org/people/1787666/overview

Dankai Wu: URI : https://loop.frontiersin.org/people/1654324/overview

Chuangang Peng: URI : https://loop.frontiersin.org/people/1728021/overview

Journal

Journal ID (nlm-ta): Front Bioeng Biotechnol

Journal ID (iso-abbrev): Front Bioeng Biotechnol

Journal ID (publisher-id): Front. Bioeng. Biotechnol.

Title: Frontiers in Bioengineering and Biotechnology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2296-4185

Publication date (Electronic): 30 January 2023

Publication date Collection: 2023

Volume: 11

Electronic Location Identifier: 1117647

Affiliations

Orthopaedic Medical Center , Second Hospital of Jilin University , Changchun, China

Author notes

Edited by: Sudarshan Singh, Chiang Mai University, Thailand

Reviewed by: Himanshu Paliwal, Ganpat University, India

Popat Mohite, St. Johns Institute of Pharmacy and Research, Palghar, India

Sankha Bhattacharya, SVKM’s Narsee Moonjee Institute of Management and Studies (NMIMS), India

*Correspondence: Dankai Wu, wudk@ 123456jlu.edu.cn ; Chuangang Peng, pengcg@ 123456jlu.edu.cn

This article was submitted to Biomaterials, a section of the journal Frontiers in Bioengineering and Biotechnology

Article

Publisher ID: 1117647

DOI: 10.3389/fbioe.2023.1117647

PMC ID: 9923112

PubMed ID: 36793443

SO-VID: 8e072397-8997-4dc8-bb90-62bf854f0072

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 06 December 2022

Date accepted : 18 January 2023

Funding

Funded by: Department of Finance of Jilin Province , doi 10.13039/501100009991;

Award ID: 2019SCZT014

Funded by: Wu Jieping Medical Foundation , doi 10.13039/100007452;

Award ID: 3D4212427429

This work was supported by Jilin Province Department of Finance (2019SCZT014) and Wu Jieping Medical Foundation (3D4212427429).

Drug delivery systems based on polyethylene glycol hydrogels for enhanced bone regeneration

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Abstract

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RNA drug delivery

Most cited references 139

Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects

Injectable and thermo-sensitive PEG-PCL-PEG copolymer/collagen/n-HA hydrogel composite for guided bone regeneration.

Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities

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